Current data in polycyclic aromatic hydrocarbon (PAH) carcinogenesis indicate multiple mechanisms of activation in tumor initiation. PAH bay-region vicinal diol epoxides have been studied as ultimate carcinogenic metabolites. Such critical intermediates as PAH radical cations, certain esters of hydroxymethyl PAH and simple PAH arene oxides, have received less attention. We propose further study of biological activation of PAH by one-electron oxidation to determine the role of PAH radical cations in carcinogenesis and to provide more evidence that one-electron oxidation may be the selective mechanism of activation in rat mammary gland by testing PAH (a) in which the diol-epoxide region has been blocked, but which can be activated by one-electron oxidation and (b) which we can predict will be active or not by one-electron oxidation. To achieve these aims we will compare carcinogenicity by direct application in mammary glands of female Sprague-Dawley rats of (1) 3-methylcholanthrene (MC), MC-8-F and MC-10-F, (2) benzo[a]-pyrene (BP), 10-azabenzo[a]pyrene, BP-6F, BP-7-F, BP-8-F, BP-9-F and BP-10-F, (3) 7, 12-dimethylbenz[a]anthracene (DMBA), DMBA-2-F, DMBA-3-F, DMBA-5-, DMBA-8-F, DMBA-9-F, DMBA-10-F and DMBA-11-F and we will determine if (4) 12-methylbenz[a] anthracene is noncarcinogenic or weakly carcinogenic as is 7-methylbenz[a]anthracene and if (5) dibenzo[a,e]pyrene, dibenzo[a,h]pyrene, dibenzo[a,i]pyrene and dibenzo[a,l]pyrene are carcinogenic. We will also study the enzymology related to PAH activationin mammary gland since we think peroxidase enzymes activate PAH there and we will measure and compare the aryl hydrocarbon hydroxylase and peroxidase acitivity in uninduced and induced rat mammary homogenates. Finally, since MC-1-OH was weakly carcinogenic in mammary gland, we postulate its activity as due to enzymatic or nonenyzmatic formation of the alkylating metabolite MC-1-OCOCH3. To determine if this is the activation mechanism for MC-1-OH, BP-6-CH2OH and BA-73-CH2OH, we plan to (1) compare in rat mammary gland the carcinogenicity of MC-1-OH vs. MC-1-OCOCH3, BP-6-CH2OCOCH3 and BA-7-CH2OH vs. BA-7-CH2OCOCH3; (2) discover whether MC-1-OH, MC-2-OH, BP-6-CH2OH and BA-7-CH2OH are acetylated nonenzymatically by [14C]acetyl-CoA and (3) evaluate the above benzylic alcohols as substrates for rat liver and mammary tissue O-acyltransferase.